The effects of dosage and the routes of administrations of streptozotocin and alloxan on induction rate of type1 diabetes mellitus and mortality rate in rats

Abstract

The approach and novelty of this scientific work was to formulate the appropriate Streptozotocin (STZ) and Alloxan dosage in different routes of administration to imply minimum mortality rate and high incidence of diabetes mellitus (DM) in the rat experiment model. Rats were randomly divided into STZ, Alloxan and control groups. 1-Alloxan group was divided into two subgroups: intraperitoneal (ip) subgroups which received a single dose of, 140, 120, 100 and 80 mg/kg; and the subcutaneous (sc) subgroups which received a single dose of, 120, 110, 100, 90, and 80 mg/kg. 2-STZ group was divided into four subgroups of ip route. The ip subgroup which received intraperitoneally a single dose of, 30, 35, 40 and 50 mg/kg. 3-The control group: This group received solo distilled water. The injection day was considered as the day zero. Blood glucose levels and mortality rate were recorded. Subsequently, 30 days after, the logistic regression modeling was used to evaluate the effect of the explanatory variables, the dose levels, and route approaches, on the probability of DM incidence, and mortality. According to the statistical logistic analysis for Alloxan, it is concluded that the minimum dosage needed to induce DM was 120 mg/kg by sc method (probability 0.712). In addition, the logistic analysis for STZ showed that the optimal dose-level for STZ was 40 mg/kg with ip with approximate induction of DM probability 0.764. Based on the data, male Wistar rats in which received a single dosage of Alloxan by sc injection at dose of 120 mg/kg showed the most desirable result of induction of type I DM; furthermore, those in which received STZ by ip injection at the dose of 40 mg/kg developed a persistent and optimal DM state characterized by high rate of DM induction and low- level of mortality.

Keywords: Type one diabetes mellitus; alloxan; intraperitoneal route; rate of diabetes induction; streptozotocin; subcutaneous route.

Figure 1. The figure illustrates the estimated probability for induction of type I DM based on Alloxan data, the logistic model, fitted separately for ip (circle symbol) and SC (triangle symbol) methods. Pursuant to the analysis, the two methods showed an increase trend for the probabilities of induction of DM over various dose levels. However, the SC method for Alloxan depicts a larger slop and hence a higher probability of induction for DM at 120mg/kg. Therefore, the more desirable choice would be the mentioned Alloxan level and SC method to induce DM in mammals. It is imperative to note, that the figure does not imply that by increasing the Alloxan dose level, more than 140mg/kg, the probability of induction of DM may also get increased, because beyond this critical level the mortality rate starts to increase rapidly.

Figure 2. Figure 2 illustrates the estimated probability data for induction of type I DM by STZ in which logistic model was used. As seen the probabilities of induction of DM first increases up to dose level 40mg/kg and then starts to decreases for higher levels. Therefore, we found that the dose level 40mg/kg with STZ by ip method was the best method to induce DM type É in the current study.